tbuckley/cabot-search huggingface dataset:
Burden of illness in metastatic colorectal cancer.
Authors: Edward Neuberger, Naomi Schwartz, Ling-I Hsu, Allison Dillon, Muriel F. Siadak
Journal: Journal of Clinical Oncology (2023)

53 Background: Current treatment options for patients with metastatic colorectal cancer (mCRC) have limited efficacy and are associated with substantial toxicity, especially for patients with mCRC refractory to standard therapies. Targeted agents may improve outcomes, compared with traditional chemotherapeutic approaches, in those patients with mCRC expressing actionable biomarkers. The objective of this study was to evaluate clinical outcomes and associated health care costs by line of therapy among patients with mCRC. Methods: A retrospective analysis of Merative MarketScan Commercial and Medicare Supplemental Administrative health claims databases was conducted. Adult patients with mCRC initiating systemic therapy between January 1, 2017 and September 30, 2021 were identified. Patient characteristics, time to discontinuation (TTD), time to next treatment (TTNT), and per-patient-per-month (PPPM) healthcare resource utilization and costs were evaluated for each line of therapy. Results: 3,455 patients with mCRC initiated systemic therapy during the study period and met all patient selection criteria. The median age at index was 56 years and median follow-up was 14 months. 1082 (31%), 372 (11%), and 185 (5%) patients went on to receive 2L, 3L, and 4L+ treatment, respectively. The most common regimens in 1-3L were as follows: 1L – FOLFOX; capecitabine, oxaliplatin; 2L - FOLFIRI+Bev; tipiracil/trifluridine; 3L – tipiracil/trifluridine; regorafenib. Median TTD in 1L through 3L was 22.0, 16.6, and 14.4 weeks, respectively. Median TTNT was 47, 26, and 21 weeks, in 1-3L, respectively. 184 (17%) and 265 (25%) of 2L patients experienced ≥1 inpatient and ≥1 emergency department (ED) visit during 2L treatment, respectively. During 2L treatment, patients had an average of 3.7±7.3 mCRC treatment-related outpatient visits per month. PPPM inpatient, ED, outpatient, and pharmacy costs are displayed. Conclusions: There is an unmet need for effective therapies in 2L+ mCRC, where clinical outcomes are poor. Later lines of therapy are associated with substantial HCRU and costs. [Table: see text]
A prospective single-arm phase II study of blank-microsphere transarterial chemoembolization (bTACE) plus lenvatinib (LEN) and sequential microwave ablation (MWA) in patients with large hepatocellular carcinoma (L-HCC, ≥ 7 cm): The Talem trial.
Authors: Zhimei Huang, Xue Han, Yiquan Jiang, Ling Gu, Tianqi Zhang, Jianwei Wang, Jinhua Huang
Journal: Journal of Clinical Oncology (2023)

567 Background: Blank-microsphere transarterial chemoembolization (bTACE) has been demonstrated to have great efficacy, low toxicities and few adverse events. We report results of efficacy, safety and immunomodulatory effects from a phase II study of bTACE plus low-dose Lenvatinib (LD-LEN) and sequential microwave ablation (MWA) in patients with large hepatocellular carcinoma (L-HCC, ≥ 7 cm). Methods: Patients with large HCC with tumor number ≤ 3 and tumor diameter ≥ 7 cm (BCLC stage A/B) were treated with bTACE plus LD-LEN (4-8mg/day) and sequential MWA. bTACE was performed using blank microspheres and low-dose chemotherapeutic agents. Peripheral blood mononuclear cells (PBMC) were isolated before and after b-TACE plus LD-LEN for the evaluation of immunomodulatory effects. The primary endpoint was objective response rate (ORR) per modified-RECIST (mRECIST) criteria. Secondary endpoints included progression free survival (PFS), overall survival (OS), down-staging rate (DSR), complications and adverse events (AEs). Results: From November 2019 to March 2022, a total of 46 patients were enrolled in the study. The ORR per mRECIST was 93.02% (CR, n=26; PR, n=14) and DSR was 83.7 (36/43). Eight patients reached CR without MWA. The 1-year and 2-year OS rates were 89.4% and 67.5%, respectively. The 1-year and 2-year PFS rates were 57.8% and 34.8%, respectively. The median PFS were 16.7 months (95% CI, 8.6-not reached). The majority of the AEs observed were grade 1-2 (n = 21, 48.8%) and no treatment related death was observed. PBMC samples from 18 patients undergoing bTACE plus LD-LEN were investigated. Among myeloid cell populations, we observed a marked decline after treatment in CD11b + CD33 + HLA-DR - MDSCs ( p &lt;0.005). Increased numbers of activated CXCR5 + CD8 + and CXCR5 + CD4 + T cells were found after treatment ( p &lt; 0.005), exerting anti-tumor immunity. Conclusions: From November 2019 to March 2022, a total of 46 patients were enrolled in the study. The ORR per mRECIST was 93.02% (CR, n=26; PR, n=14) and DSR was 83.7 (36/43). Eight patients reached CR without MWA. The 1-year and 2-year OS rates were 89.4% and 67.5%, respectively. The 1-year and 2-year PFS rates were 57.8% and 34.8%, respectively. The median PFS were 16.7 months (95% CI, 8.6-not reached). The majority of the AEs observed were grade 1-2 (n = 21, 48.8%) and no treatment related death was observed. PBMC samples from 18 patients undergoing bTACE plus LD-LEN were investigated. Among myeloid cell populations, we observed a marked decline after treatment in CD11b + CD33 + HLA-DR - MDSCs ( p &lt;0.005). Increased numbers of activated CXCR5 + CD8 + and CXCR5 + CD4 + T cells were found after treatment ( p &lt; 0.005), exerting anti-tumor immunity. Clinical trial information: NCT05555316 .
A phase II clinical trial to study the use of cabozantinib (cabo) in patients with hepatocellular carcinoma (HCC) post immunotherapy treatment.
Authors: Stephen Lam Chan, Baek-Yeol Ryoo, Frankie Mo, Jaekyung Cheon, Leung Li, Kwan H. Wong, Nicole Yim, Hyeyeong Kim, Changhoon Yoo
Journal: Journal of Clinical Oncology (2023)

571 Background: There has been a lack of prospective clinical trial data on subsequent treatment after immune checkpoint inhibitor (ICI)-based treatment in HCC. To address this question, we designed and completed a phase II multicentred study to evaluate the use of cabo in HCC after prior ICI-based treatment. Methods: This is an investigator-initiated clinical trial involving 3 academic centres in Hong Kong and Korea. Key eligibility criteria include confirmed diagnosis of HCC; refractoriness to prior ICI-based treatment; duration of prior ICI-based treatment ≥2 months; Child's A liver function; ECOG performance status 0-2; maximal 2 lines of therapy. All patients (pts) were started cabo at 60mg once daily to progressive disease or intolerable toxicity. The primary endpoint is progression-free survival (PFS). Other secondary endpoints including response rate (RR) according to the RECIST, overall survival (OS) and treatment-related adverse event (TRAE). Total sample size is 48 (one-sided alpha 0.05; power 80%). Results: Total 48 pts were recruited from Oct 2020 to May 2022. Data were frozen on 1 Aug 2022 for analyses. The median follow-up was 11.2m. Seven (14.9%) pts remained on treatment; 1pt was found to ineligible and excluded from the analysis. The median age is 61 (Range 36-83). Aetiology of HCC: HBV 34 (72.3%); HCV 2 (4.3%); alcoholic 8 (17%); Most pts have BCLC stage C (93.6%). All pts have Child’s A liver function. Total 39 (83%) pts receive ICI-based first-line therapy, and 19 (40.4%) pts have prior atezolizumab-bevacizumab (AB) treatment. The median PFS is 4.1m (95% CI 3.3-5.3). Regarding RR, PR and SD occurs in 3 (6.4%) and 36 (76.6%) pts, respectively. The median OS is 9.9m (95% CI 7.3-14.4) and the 1-year survival rate is 45.3%. Amongst the 19 pts receiving prior AB treatment, the median OS is 14.3m (95% CI: 5.5-14.4) with 1-year survival rate of 50.7%. For non-AB regimen, the median OS is 8.9m (95% CI 6.1-NR) with 1-year survival rate of 42.0%. Commonest G3-4 TRAE is thrombocytopenia (6%); hypertension (4%) and ALT elevation (4%).The median dose of cabo is 41.6mg per day (range: 24.3-60.0 mg). Conclusions: Post-ICI use of cabo is associated with a median PFS of 4.1m and median OS of 9.9m. AB-cabo sequence appears to have more favourable outcome than non-AB-cabo sequence. No new safety signals were observed. This clinical trial reports the first prospective post-ICI survival data on TKI. Clinical trial information: NCT04588051 .
Phase 1b study to assess the safety of neoadjuvant trifluridine/tipiracil with concurrent radiation in resectable stage II/III rectal cancer.
Authors: Emerson Yu-sheng Chen, Nima Nabavizadeh, Daniel Herzig, Elena Korngold, Adel Kardosh, Guillaume Joe Pegna, Kenneth Gregory Bensch, Eric C. Anderson, Vassiliki Liana Tsikitis, Kim Lu, Skye C. Mayo, Brian Brinkerhoff, Shaun Goodyear, Melissa Wong, Anne Fahlman, Erin Taber, Johnson Vo, Charles R. Thomas, Charles D. Lopez
Journal: Journal of Clinical Oncology (2023)

TPS274 Background: Treatment of locally advanced rectal cancer currently involves tri-modal therapy with pre-operative chemo-radiation (CRT), surgery, and combination chemotherapy. Total neoadjuvant therapy (TNT) is emerging as an important treatment pathway that can increase rates of complete response (CR) leading to better overall outcomes. Novel radio-sensitizing agents may improve rates of CR. Trifluridine/tipiracil (TFD/TPI) is a novel fluoropyrimidine that has demonstrated clinical efficacy in patients with treatment-refractory metastatic colorectal cancer. Importantly, TFD/TPI has superior radio-sensitization in vitro compared to 5-fluorouracil, and we hypothesize that this can improve the tumor response of patients. This phase 1 study assesses the safety and preliminary efficacy of using TFD/TPI for long-course CRT for rectal cancer followed by FOLFOX chemotherapy in the TNT setting. Methods: NCT04104139 is a prospective, dose-finding phase I study using Bayesian Optimal Interval (BOIN) design to determine the maximum tolerated dose (MTD) of TFD/TPI with concurrent standard dose/fractionation radiation for resectable rectal cancer. Adults with previously untreated rectal adenocarcinoma, with clinical stage II (T3-4aN0) and stage III (T1-4aN1+) by MRI and endoscopy are eligible. Patients must first receive CRT with standard radiation (45-50 Gy over 25-28 fractions) followed by up to 8 cycles of standard FOLFOX, or alternatively 5 cycles of CAPOX chemotherapy. During CRT, the first dose level of TFD/TPI is PO 25mg/m2 twice a day from Mon to Fri (5 weekdays) alternating on weeks 1, 3, and 5 concurrent with 5-6 weeks of radiation. The second dose level is 30mg/m2, and third dose level is 35mg/m2. The MTD of TFD/TPI in combination with radiation is the dose corresponding to a dose limiting toxicity (DLT) probability of 30% using the BOIN design with escalation/de-escalation of each dose level occurring in cohorts of 3 participants until a maximum total of 18 participants, sub-total of 12 patients within one dose level, or another stopping rule based on serious toxicities. The primary endpoint is proportion of DLTs for TFD/TPI at MTD. Secondary endpoints include overall tolerability profile, delayed toxicities during FOLFOX, rates of clinical CR, rates of pathologic CR, and correlative biomarkers. The study was activated December 2019 and has accrued 8 of intended 18 patients. Clinical trial information: NCT04104139 .
A multicenter randomized controlled trial of esophagectomy with or without prophylactic supraclavicular node dissection: A phase III trial (JCOG2013, MODERN3).
Authors: Shigeru Tsunoda, Yasuhiro Tsubosa, Keita Sasaki, Ryunosuke Machida, Hiroyuki Daiko, Ken Kato, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2023)

TPS474 Background: Supraclavicular lymph nodes (SCLN) have been regarded as regional nodes of thoracic esophageal cancer in Japan and resected along with cervical paraesophageal lymph nodes as a cervical part of the standard three-field dissection, while the involvement of SCLN is regarded as distant metastasis in Western countries. However, there is no clear evidence that supports or rejects prophylactic SCLN dissection. As postoperative SCLN metastasis can often be managed by either surgery or chemoradiotherapy at the time of relapse, routine prophylactic SCLN dissection may not be essential. Here we conduct the clinical trial to confirm the non-inferiority of esophagectomy with D2 lymphadenectomy except for SCLN to standard D2 lymphadenectomy in terms of overall survival (OS) for patients with resectable upper or middle thoracic esophageal cancer. Methods: Eligibility criteria include the followings; upper or middle thoracic esophageal squamous cell carcinoma, adenosquamous carcinoma, or basaloid cell carcinoma with clinical stage I, II, III, or IVA (except for T4) based on the 8th UICC-TNM, age 18 to 80, ECOG performance status 0 or 1, and adequate organ function. Neoadjuvant chemotherapy (cisplatin plus 5- fluorouracil or docetaxel plus cisplatin plus 5-fluorouracil) is allowed, but preoperative chemoradiotherapy is not allowed. Patients are randomly assigned to the following two arms using the minimization method with a random component to balance institution, clinical stage (Stage I (T1N0M0) versus Stage I (T1N1M0)/II/III/IVA), age (76 or older versus 75 or younger), and tumor location (upper thoracic versus middle thoracic). Patients undergo either esophagectomy with standard D2 dissection (Arm A) or esophagectomy with D2 lymphadenectomy except for SCLN (Arm B). The primary endpoint is OS in all randomized patients. The secondary endpoints are relapse-free survival, the incidence of perioperative and delayed complications, the incidence of SCLN recurrence, the incidence of salvage cervical treatment, the proportion of synchronous cervical and abdominal procedure, and operation time and the number of operating surgeons. A sample size of 456 patients would be required to observe 147 events to demonstrate the non-inferiority of Arm B in terms of OS, with a one-sided alpha of 5%, power of 70%, an accrual period of 5 years, a follow-up period of 3 years, and a non-inferiority margin of 6% at 3-year OS, assuming the expected 3-year OS of Arm A and Arm B are 80% and 81%, respectively. The planned sample size was set at 480 patients (240 patients per arm). This trial was registered at the Japan Registry of Clinical Trials (jRCT) as study number jRCT1030220248 and started in August 2022. Clinical trial information: jRCT1030220248 .
A single center survival analysis of patients with colorectal cancer who underwent next generation sequencing.
Authors: Lucyna Krzywon, Anthoula Lazaris, Andrea Gomez, Jennifer Kalil, Oran Zlotnik, Peter Metrakos
Journal: Journal of Clinical Oncology (2023)

31 Background: Colorectal cancer (CRC) remains a lethal diagnosis with an overall 5-year survival rate of 5-10% for patients with unresectable metastatic disease. The advent of next generation sequencing allows tailored systemic therapy to specific mutations with the goal of improving patient survival. McGill University Health Center instituted next generation sequencing in 2019. Our study aims to evaluate survival outcomes in patients who underwent NGS testing. Methods: A retrospective collection of data on all patients with CRC who were presented at both lower gastroenterology and hepatobiliary tumor boards from January 2019 through July 2022 ( n= 498). Survival and was compared between patients who were found to have genetic alterations identified using the Illumina Miseo platform. Statistical Analysis was performed with GraphPad Prism. Results: A total of 321 (64%) patients had NGS performed on either their primary tumor or a metastasis. A total of 229 (71%) CRC patients had genetic alterations identified on NGS. The most commonly mutated genes were KRAS (41%), APC (17%), PIK3CA (16%) and BRAF (8%). There was no significant difference in median overall survival between patients who had an identified genetic alteration and patients who did not (p = 0.8). Patients with metastatic disease and synchronous presentation had higher rates of genetic alterations (69% and 70%, respectively). Conclusions: This study provides real world data for a single institution initiating Next generation sequencing in colorectal cancer patients. Next Generation testing is an advantageous tool which can help stratify patients into tailored treatment regiments which will lead to improved patient outcomes.
Lower risk of metabolic syndrome and fatty liver in gastric cancer survivors: A propensity score-matched analysis.
Authors: Hyojin Park
Journal: Journal of Clinical Oncology (2023)

334 Background: With the recent development in cancer treatments, the number of cancer survivors is rapidly increasing. Thus, evaluation and management of accompanied comorbidities as well as survival itself have become important issues in cancer survivors. The aim of this study was to investigate the prevalence and risk of metabolic syndrome (MetS) and fatty liver in gastric cancer (GC) survivors compared with that in non-cancer (NC) subjects. We also analysed the risk for metabolic dysfunction-associated fatty liver disease in GC survivors compared with that in NC subjects. Methods: In this cross-sectional study, participants who visited Gangnam Severance Hospital from 2014 to 2019 for health check-ups were enrolled. After age- and sex-matched 1:4 propensity score matching, 119 GC survivors and 476 NC subjects were included. GC survivors were divided into operated gastric cancer survivors (OpGC) (n=95) and non-operated survivors (non-OpGC) (n=24). MetS was diagnosed by metabolic components and FL was assessed by ultrasonography. Results: MetS was observed in 21.0% of GC survivors and 30.5% of NC subjects, and in 13.7% of OpGC survivors and 50.0% of non-OpGC survivors. FL was observed in 25.2% of GC survivors and 37.6% of NC subjects, and in 21.1% of OpGC survivors and 41.7% of non-OpGC survivors. After adjusting for age, sex, MetS risk was significantly lower in OpGC survivors (odds ratio [OR] = 0.377, 95% confidence interval [CI]: 0.200-0.711, P=0.003). FL risk was significantly lower in OpGC survivors (OR = 0.467, 95% CI: 0.267–0.816, P=0.007), but not in non-OpGC survivors, compared with NC subjects. Risk of metabolic dysfunction-associated fatty liver disease was significantly lower in OpGC survivors (OR = 0.412, 95% CI: 0.233–0.729, P=0.002) compared with NC subjects. Conclusions: OpGC survivors showed a lower risk of MetS and FL compared with NC subjects. These associations can be explored to ensure timely medical intervention in GC survivors.
Impact of chemotherapy on COVID-19 vaccination in patients with gastrointestinal cancer.
Authors: Mitsukuni Suenaga, Shinichi Yamauchi, Yuya Sato, Rika Noji, Ryo Morikawa, Yoshihito Kano, Masanori Tokunaga, Yusuke Kinugasa
Journal: Journal of Clinical Oncology (2023)

32 Background: Multiple doses of vaccine against COVID-19 provide cancer patients with the opportunity to continue their cancer treatment. We previously reported the results that COVID-19 vaccination are tolerable, and treatment schedule changes could be minimized in gastrointestinal (GI) cancer patients receiving chemotherapy. In the present study, we investigated the differences in the occurrence of vaccine-related adverse events (AEs) in patients receiving chemotherapy and those not receiving chemotherapy. Methods: 141 patients with GI cancer who had two doses of mRNA COVID-19 vaccine (Pfizer-BioNTech or Moderna) between May 2021 and April 2022 with sufficient data on vaccination were included in this retrospective observational study at the Tokyo Medical and Dental University hospital. This study combined two different cohorts: an evaluation cohort of 89 patients (median age 70 years, male 57.8%) receiving chemotherapy; and a control cohort of 52 patients under follow-up after radical surgery (median age 68.5 years, male 69.2%). All patients had no history of COVID-19 infection. Treatment- and vaccine-related AEs were recorded by outpatient interviews and self-reports. Results: Patient characteristics of the two cohorts were similar except for the location of primary tumor: colorectal (80.9% vs 7.7%) and gastric (15.7% vs 88.5%). There were no significant differences in comorbidities between the cohorts (67.4% vs 55.8%). In the evaluation cohorts, 65 patients (73.0%) had vaccine-related AEs: injection site pain (68.5%), fever (9.0%), fatigue (6.7%), headache (3.4%), gastrointestinal symptoms (2.2%), redness (1.1%) and sleepiness (1.1%) after the first dose; and 66 patients (74.2%) had vaccine-related AEs with increased rate of fever (32.6%) and fatigue (19.1%) after the second dose. In the control cohort, vaccine-related AEs occurred in 28 (53.8%) after the first dose and 37 (71.2%) patients after the second doses, and similarly, fever and fatigue increased after the second dose. There were no significant differences in the number of vaccine-related AEs and their changes between cohorts. There was no treatment- and vaccine-related deaths. Conclusions: The results of this study suggest that systemic chemotherapy in patients with GI cancer does not have a marked negative effect on COVID-19 vaccination.
Phase 2 study of cabozantinib (cabo) and pembrolizumab (pembro) in metastatic gastric/gastroesophageal adenocarcinoma (mGEA) refractory to immune checkpoint inhibitors (ICIs).
Authors: Farshid Dayyani, Kristian Ghio, Fa-Chyi Lee, May Thet Cho, Joseph Chao, Thomas H Taylor, Kristen Neumann
Journal: Journal of Clinical Oncology (2023)

345 Background: Most mGEA patients (pt) progress on therapy including ICI, with about 5% progression-free at 6mo (PFS-6) with single agent ICI in later lines of therapy. Alternative therapeutic approaches are needed. Cabo is a multi-tyrosine kinase inhibitor which might modulate immunosuppression in the tumor microenvironment. This study reports on safety and efficacy of the combination of Cabo+Pembro in mGEA refractory to ICI. Methods: Investigator-initiated, single‐arm, two-stage, single institution, phase 2 study in pts with mGEA after ≥1L of fluoropyrimidine and platinum-containing regimens. Additionally, pts with a PD-L1 CPS score ≥10% had also progressed on ICI. Cabo dose was 40mg p.o. daily on days 1 through 21 of a 21‐day cycle, with Pembro 200 mg i.v. on day 1. The primary endpoint was PFS-6, with H0=5%, Ha≥20%. Stage one results (n=19) exceeded the futility threshold. The complete design requires 27 evaluable pts and n≥4 pts with PFS-6 to reject H0 in favor of Ha. Results: 25 pts are currently enrolled. Because stage one did not signal futility, enrollment continues. Median age 58 years (24-75), female (n=13), ECOG 0/1= 13/12, GC/GEJ= 14/11, Caucasian/Hispanic/Asian/other = 7/7/8/3. After a median follow-up of 5.1mo (1.2-24.6), the median PFS and OS are 2.9mo (95% CI 2.1-4.6) and 9.5mo (95% CI 3.1-14.6), respectively. 11/25 had disease progression on or before the first imaging timepoint at 8 weeks, i.e. the clinical benefit rate is 56% (14/25). 13/20 pts had measurable disease by RECISTv1.1: PR 1(7.7%), SD 7(41.2%), PD 5(38.5%). The most common any grade (G) treatment related adverse events (TRAE) were diarrhea (28%), fatigue (20%), and hypertension (16%). G3-4 TRAE were seen in n=3 pts (Hypertension, Thromboembolic event, esophageal perforation; each n=1). No G5 were reported. Conclusions: In this interim analysis of this ongoing study, the combination of Cabo+Pembro shows promising clinical benefit with an estimated OS of 9.5mo in mGEA pts resistant to prior ICI. Follow-up of the primary endpoint is ongoing. The regimen appears tolerable with no new safety signals. More mature data including the primary endpoint and correlative studies will be presented at the meeting. Clinical trial information: NCT04164979 .